Method for preparing particles of a defined size in a reaction vessel

ABSTRACT

The present invention relates to a method of preparing particles of a defined size and morphology, using a reaction of reactants, wherein the reaction is carried out in the presence of rotational forces and wherein the reactants are separated from each other by means of a contactor. The present method is suitable for preparing articles having a particle size from 10-2000 nm.

The present invention relates to a method of preparing particles of adefined size, using a reaction of reactants in a reaction vessel.

From International application WO 01/45830 there is known a tubularapparatus comprising a reaction vessel for accommodating a first phaseand at least one membrane for accommodating a second phase. Only themembrane, which is positioned to be coaxial with the tubular reactor, issuitable for rotation, and after rotation of the membrane the secondphase is controllably dispersed into the first phase. A drawback of sucha construction is the fact that a precise and costly seal is required toprevent leakage of reactants. In addition, a uniform particle sizedistribution is not ensured during the start-up phase when such a methodis used, which has an adverse effect on the reproducibility.

European patent application No. 0 157 156 relates to a continuousprocess for making manganese carbonate which is obtained byprecipitating it from a manganese(II) salt solution by means of adiammonium carbonate solution, which reaction takes place whilestirring.

Japanese patent publication JP-63-023734 relates to a method ofpreparing small particles, wherein a tubular reactor is used, in whichreactor an inner tube having a smaller diameter is coaxially disposed. Areactive gas A is introduced into the central tubular reactor, in whichreactor an inner tube having a smaller diameter is coaxially disposed,whilst a reactive gas B is supplied to the annular space formed betweenthe inner tube and the tube surrounding said inner tube. An overpressurecauses the reactive gas B to pass through the porous wall of the innertube, resulting in a reaction between the reactive gas A and thereactive gas B.

Such a method is known, for example from U.S. Pat. No. 5,674,531,wherein nanoparticles are obtained by dissolving an active substance,e.g. insulin, and the ketalized polytartramidic acid separately, mixingthe solutions obtained and introducing the mixture into a precipitatingagent through a cannula having an external diameter of 0.2 to 1.2 mm,bonding the nanoparticles obtained to one or more ligands and finallyfiltering the nanoparticles through a filter having a pore size of 0.2μm to 0.8 μm. From U.S. Pat. No. 5,840,111 there is furthermore known aprocess for producing a particulate nanodisperse titanium oxide having amaximal particle size distribution of between 1 and 10 nm, which processcomprises the steps of mixing of solution comprising sulphuric acid andtitanyl sulphate at an elevated temperature and an alkaline-reactingliquid until the mixture reacts to form titanium dioxide nanoparticles,cooling the obtained mixture and adding a monobasic acid to thethus-cooled mixture, causing the titanium dioxide nanoparticles toflocculate, recovering the resulting titanium dioxide nanoparticlesflocculate, and finally washing the flocculate with a monobasic acid toobtain a precipitate. A drawback of the two aforesaid methods is thefact is that several reaction steps are required in order to obtainparticles of a defined size. The use of several separate steps generallyhas an adverse effect on the reproducibility. Moreover, a slight loss ofstarting material will occur with every step, so that the yield ofparticles of a defined size will decrease.

Another known method of preparing nanoparticles is the use of reversedmicro emulsions. This technique also has as a number of drawbacks,however. After all, micro emulsion processes are difficult to scale up,and another drawback is the fact that particles can only be obtained ina limited range of sizes.

One aspect of the present invention is to provide a method of preparingparticles of a defined size and morphology, which method overcomes theaforesaid drawbacks of the prior art.

Another aspect of the present invention is to provide a method ofpreparing particles of a defined size and morphology, which method isconsidered to be suitable for preparing particles of a size ranging from10-3000 nm.

Another aspect of the present invention is to provide a method ofpreparing particles of a defined size and morphology, wherein particleshaving a very specific particle size distribution are obtained.

The method as referred to in the introduction is characterized in thatthe reaction vessel is rotated, so that the reaction is carried out inthe presence of rotational forces, wherein the reactants are separatedfrom each other by means of a contactor, which contactor is soconstructed that one reactant is contacted with the other reactant(s)under controlled conditions after it has passed the contactor, so as toform the reaction product, wherein the density of the reaction productthus formed is greater than that of the medium in which it has beenformed.

The present method is relatively easy to scale up, and an importantadvantage is the fact that no auxiliary materials such as surfactants ororganic solvents are required. Thus a clean and simple method isprovided for obtaining particles of a defined size. The present methodthus employs a rotational force for preparing particles on the one handand for removing particles from the reaction zone on the other hand. Thepresent method is in particular suitable for preparing particles ofvarying size and morphology and having a very uniform particledistribution. The special size of a particular particle depends, amongother things, on the density of the starting materials, the rotationalforce that is employed, the temperature, the differences in density, theconcentrations of reactants, the viscosity, the reaction time and thetype of contactor, for example hydrophobicity, the pore size, thethickness of the contactor and the like. The products obtained by usingthe present method can be used for various purposes, for example in theproduction of semiconductors, pigments, catalytic converters and displayscreens.

The contactor used in the present invention is preferably selected fromthe group consisting of membrane, diaphragm, filter and atomizer,wherein in particular a membrane having a defined pore size is used.Such a contactor can be considered to be an element which keeps thereactants separated, but which subsequently makes it possible, after arotational force has been exerted on the reaction vessel, to contactsaid one reactant with the other reactant(s) under controlled conditionsafter it has passed the contactor, so as to form the reaction product.In a specific embodiment, a number of contactors disposed one behindanother, seen in the longitudinal direction of the reaction vessel, maybe present in the reaction vessel.

In order to ensure that the reaction product being formed exits thereaction zone within a specific period of time, it is preferred to use arotational force having an acceleration of at least 1000 g. If arotational force having a value lower than 1000 g is used, the residencetime of the reaction product in the reaction zone will be too long, as aresult of which reaction products having a wide particle sizedistribution are obtained, which is undesirable.

The rotational forces employed in the present invention are preferablygenerated by carrying out the reaction in a centrifuge, with theselection of a specific centrifuge taking place in dependence on thedesired rotation range. It should be understood that both the reactionvessel and the contactor present therein as well as the reactants aresubject to rotational forces.

In order to obtain a precisely defined size of the reaction product, itis preferred to use a membrane having a molecular weight cut-off (MWCO)of maximally 500 kDa, in particular maximally 50 kDa, especiallypreferably maxially 3 kDa. When the aforesaid parameters are suitablyset, the particle size of the reaction products formed by the reactionwill range from 10-3000 nm, preferably said size will be less than 300nm, in particular less than 50 nm.

In a preferred embodiment it is desirable for the reaction vessel to beof substantially circular cross-section, and for the contactor to extendover the entire cross-section of the reaction vessel, perpendicularly tothe longitudinal axis thereof. When such a construction is used, aproduct of well-defined size and morphology is obtained, and in additiona specific particle size is achieved.

It should be understood that the present invention is not limited toliquids, but that any phase, viz the gas phase, the solid phase, theliquid phase and the supercritical phase, may be used both for the phaseabove the contactor and for the phase below the contactor, as long asthe density of the reaction product that has been formed is greater thanthe density of the medium in which it has been formed. If two liquidsseparated by a contactor are used, wherein the contactor is e.g. anultrafiltration membrane having a molecular weight cut-off (MCWO) ofless than 100 kDa, which liquids are contacted with each other, theliquid present above the contactor will penetrate through theultrafiltration membrane as a result of the action of the rotationalforces and thus be added to the liquid present under the contactor in acontrolled manner. The size of the droplets of the liquid from above thecontactor in the lower liquid is determined by the properties of the twoliquids and those of the contactor. In the contact layer positioneddirectly below the ultrafiltration membrane, the droplets passingthrough the membrane react with the liquid already present to formreaction products having a density greater than that of the medium, inparticular the lower liquid in which the reaction takes place. Theparticles thus formed are removed from the reaction zone as a result ofthe action of the rotational forces that occur. In a specific embodimentit is desirable for an additional layer or phase to be present on top ofthe upper layer of reactants, in particular in order to preventevaporation of active components from the layers of liquid.

It is in particular preferable for the proportion between the density ofthe reaction product being formed and the density of the medium in whichthe reaction product is being formed by means of the reaction to be atleast 1.5:1, in particular for the proportion between the density of thereaction product being formed and the density of the medium in which thereaction product is being formed by means of the reaction to be at least2:1.

The present invention is in particular suitable for forming inorganicparticles belonging to the group of oxides, carbonates, sulphides,halogenides and cyanides of one or more metals, or combinations thereof.

The present invention furthermore relates to particles obtained bycarrying out the present method, wherein the particles have a particlesize ranging from 10-3000 nm and wherein said particles have a uniformparticle size distribution.

The present invention furthermore relates to a device comprising areaction vessel in which reactants separated by means of a contactor arepresent, which reaction vessel is suitable for rotation and wherein onereactant is contacted with the other reactant(s) under controlledconditions in the presence of rotational forces after it has passed thecontactor. Preferably, the reaction vessel is of substantially circularcross-section, and the contactor extends over the entire cross-sectionof the reaction vessel, perpendicularly to the longitudinal axisthereof.

Using the present method, it is possible to control the geometric shapeof the obtained reaction products, and in specific embodiments it ispossible to obtain particles having a spherical shape or particleshaving a cubic shape.

The present invention will be explained hereinafter by means of a numberof examples and Figures, in which connection it should be noted,however, that the present invention is by no means limited to suchspecial examples.

FIGS. 1-5 are images obtained by means of a Scanning Electron Microscope(SEM) of particles obtained by using the present methods.

FIG. 6 is an image obtained by means of a Transmission ElectronMicroscope (TEM) of particles obtained by using the present method.

EXAMPLE 1

A reaction vessel having a volume of 10 ml was first filled with 2 ml of0.75 M NH₄CO₃ (aq), which lower phase was separated by means of amembrane having a MWCO of 10 kDa from an upper phase consisting of 5 mlof 0.5 M MnSO₄ (aq). The reaction vessel was placed in a centrifuge andthe whole was rotated for 30 minutes, using a rotational force of 1500 gand a temperature of 30° C. Upon completion of said rotation step, thedesired product MnCO₃ (s) and NH₄SO₄ (aq) was obtained, and the MnCO₃was analysed by means of a Scanning Electron Microscope (SEM). The datafrom the analysis showed that monodisperse cubic MnCO₃ particles havinga diameter of 1600 nm had been obtained (see FIG. 1).

EXAMPLE 2

The same operations as in Example 1 were carried out, with thisdifference that a membrane having a MWCO of 30 kDa was used. Theobtained reaction product MnCO₃ was analysed by means of a ScanningElectron Microscope (SEM), and the data from the analysis showed thatdisperse cubic MnCO₃ particles having a diameter of 800-3000 nm had beenobtained (see FIG. 2).

EXAMPLE 3

The same operations as in Example 1 were carried out, with thisdifference that a rotational force of 3000 g was used. The obtainedreaction product MnCO₃ was analysed by means of a Scanning ElectronMicroscope (SEM), and the data from the analysis showed thatmonodisperse spherical MnCO₃ particles having a diameter of 700 nm hadbeen obtained (see FIG. 3).

EXAMPLE 4

The operations of Example 3 were repeated, with this difference that amembrane having a MWCO of 30 kDa was used. The obtained reaction productMnCO₃ was analysed by means of a Scanning Electron Microscope (SEM), andthe data from the analysis showed that disperse spherical MnCO₃particles having a diameter of 500-1000 nm had been obtained (see FIG.4).

EXAMPLE 5

The same operations as in Example 1 were carried out, with thisdifference that a membrane having a MWCO of 3 kDa and a rotational forceof 4500 g were used. The obtained reaction product MnCO₃ was analysed bymeans of a Scanning Electron Microscope (SEM), and the data from theanalysis showed that monodisperse cubic MnCO₃ particles having adiameter of 200 nm had been obtained (see FIG. 5).

EXAMPLE 6

The same operations of Example 5 were repeated, with this difference arotational force of 30.000 g was used for 60 minutes. The obtainedproduct MnCO₃ was analysed by means of a Scanning Electron Microscope(SEM), and the data from the analysis showed that monodisperse cubicMnCO₃ particles having a diameter of 20 nm had been obtained.

EXAMPLE 7

The same reaction vessel as in Example 1 was first filled with 2 ml of0.05 M KBr (aq) and then, after placement of a membrane having a MWCO of3 kDa, with 0.5 ml of 0.03 M AgNO₃ (aq). After rotation for 30 minutes,using a rotational force of 4500 g, the desired product AgBr (s) andKNO₃ (aq) was obtained, after which AgBr was analysed by means of aScanning Electron Microscope (SEM). The data from the analysis showedthat monodisperse spherical AgBr particles having a diameter of 300 nmhad been obtained.

EXAMPLE 8

The same operations of Example 7 were repeated, with this differencethat KBr and AgNO₃ were used in amounts of 1 ml and 0.25 respectively.In addition, a rotational force of 30.000 g was used for 60 minutes. Theobtained product AgBr was analysed by means of a Transmission ElectronMicroscope (TEM), and the data from the analysis showed thatmonodisperse spherical AgBr particles having a diameter of 30 nm hadbeen obtained (see FIG. 6).

EXAMPLE 9

A reaction vessel having a volume of 120 ml was first filled with 40 mlof 0.75 M NH₄CO₃ (aq), which lower phase was separated, by means of anatomizer, from an upper phase consisting of 20 ml of 0.5 M MnSO₄ (aq).The reaction vessel was placed in a centrifuge and rotated for 30minutes, using a rotational force of 2000 g and a temperature of 30° C.Upon completion of the rotation step, the desired product MnCO₃ (s) andNH₄SO₄ (aq) was obtained, and the MnCO₃ was analysed by means of aScanning Electron Microscope (SEM). The data from the analysis showedthat disperse cubic MnCO₃ particles having a diameter of 1500-2500 nmhad been obtained.

1. A method of preparing particles of a defined size, the methodcomprising: providing a reaction vessel having a first reactant spaceand a second reactant space, the spaces being separated by a contactor;introducing a first liquid reactant in the first reactant space;introducing a second liquid reactant in the second reactant space;rotating the reaction vessel so that the first reactant space isradially inside and the second reactant space is radially outside;forming first reactant droplets when the first reactant passes thecontactor under influence of a centrifugal force caused by the rotatingof the reaction vessel; transporting the droplets of the first reactantto the second reactant in the second reactant space under influence ofthe centrifugal force; forming a reaction product in the form ofparticles when the first reactant has been brought into contact with thesecond reactant, the reaction product having a density that is greaterthan that of the second reactant; and transporting the reaction productparticles to a radially outward end of the second reactant space due tocentrifugal forces.
 2. A method according to claim 1, characterized inthat a contactor selected from the group consisting of membrane,diaphragm, filter and atomizer is used.
 3. A method according to claim2, characterized in that a membrane having a defined pore size is used.4. A method according to claim 1, characterized in that a rotationalforce having an acceleration of at least 1000 g is used.
 5. A methodaccording to claim 1, characterized in that said rotational forces aregenerated by carrying out the reaction in a centrifuge.
 6. A methodaccording to claim 1 characterized in that a membrane of maximally 500kDa is used.
 7. A method according to claim 6, characterized in that amembrane of maximally 50 kDa is used.
 8. A method according to claim 7,characterized in that a membrane of maximally 3 kDa is used.
 9. A methodaccording to claim 1, characterized in that the size of the reactionproducts formed by the reaction ranges from 10-3000 nm.
 10. A methodaccording to claim 1, characterized in that the size of the reactionproducts formed by the reaction is<300 nm.
 11. A method according toclaim 1, characterized in that the size of the reaction products formedby the reaction is<50 nm.
 12. A method according to claim 1,characterized in that the reaction products formed by the reaction havea uniform particle size distribution.
 13. A method according to claim 1,characterized in that the reactants are in the liquid phase.
 14. Amethod according to claim 1, characterized in that the proportionbetween the density of the reaction product being formed and the densityof the medium in which the reaction product is being formed by means ofthe reaction is at least 1.5:1.
 15. A method according to claim 1,characterized in that the proportion between the density of the reactionproduct being formed and the density of the medium in which the reactionproduct is being formed by means of the reaction is at least 2:1.
 16. Amethod according to claim 1, characterized in that inorganic particlesare formed by the reaction.
 17. A method according to claim 16,characterized in that said inorganic particles belong to the groupconsisting of oxides, carbonates, sulphides, halogenides and cyanides ofone or more metals, or combinations thereof.
 18. A method according toclaim 1, characterized in that the reaction comprises a precipitationreaction.
 19. A device comprising a reaction vessel including acontactor that separates a first reactant space for holding a firstliquid reactant and a second reactant space for holding a second liquidreactant, the reaction vessel being rotatably mounted so that, when thereaction vessel rotates the first reaction space is radially inside andthe second reactant space is radially outside, the contactor beingconfigured for forming first reactant droplets when the first reactantpasses the contactor under influence of a centrifugal force caused bythe rotating of the reaction vessel.